Non-Invasive Early Warning System of Systemic Hypoperfusion: Circulatory Shock and Sepsis
by Michael R. Pinsky, MD and Jacques Creteur, MD
The Problem: Circulatory shock is defined as an inadequate oxygen (O2) delivery to tissue to sustain metabolic demand. If arterial oxygen content is adequate, then tissue ischemia develops only at the very extremes of low blood flow. Well before that time, normal physiologic adaptive mechanisms controlled by the autonomic nervous system and mediated primarily through increased sympathetic tone tend to sustain an adequate central arterial blood pressure despite falling total blood flow. Once this regulatory process is exhausted, however, systemic hypotension develops. Thus, systemic hypotension, defined as a mean arterial pressure <65 mmHg or a systolic arterial pressure <90 mmHg, occurs late in shock when tissue hypoperfusion is already compromising metabolic function. If circulatory shock associated with systemic hypotension persists, then generalized tissue ischemia manifests as end-organ failure, lactic acidosis and autonomic failure. If the bedside clinician waits for systemic hypotension to recognize circulatory insufficiency before treating their patient for circulatory shock, then he will have waited too long.
Tissue CO2 as a Solution: What is needed is a monitoring device that can identify decreasing tissue blood flow prior to impaired metabolic function. Since tissue can sustain oxidative phosphorylation (the central process of energy production of the cell) well into low blood flow states, both O2 extraction by the tissue and carbon dioxide (CO2) production remain relatively constant in a tissue bed as local blood flow initially declines. Although tissue O2 can be measured, owing to the heterogeneity of metabolic rates and the slow diffusion of O2 into the tissues from the blood, its measure to assess early forms of circulatory shock is poor. CO2 can also be measured and, in contrast to O2 measurement, changes in tissue CO2 levels can accurately track changes in local blood flow within physiologic limits owing to the high diffusing capacity of CO2 to cross lipid barriers and fluid spaces. Thus, a device that measures tissue CO2 levels could be very helpful in identifying early shock, as CO2 levels will rise well before tissue ischemia. This same device could be used to tract the effectiveness of resuscitation efforts, as CO2 levels will decline to their baseline values again once local blood flow returns to its baseline values.
Buccal CO2 as a Measure of Convenience: The oral mucosal constitutes an ideal site to measure tissue CO2, especially if the sensing probe is isolated from ambient air and can be seated in a patient’s mouth with minimal discomfort. Numerous studies have documented that both sublingual and buccal mucosal CO2 levels track circulatory stress in a quantitative fashion. In experimental models of hemorrhagic shock, sublingual CO2 levels rapidly rise before hypotension develops and fall during resuscitation only after total cardiac output is restored, even though blood pressure is restored earlier.
All forms of circulatory shock, if associated with an initial decrease in cardiac output, will be associated with a rise in buccal CO2, and this rise will occur early during the adaptive stage of shock when blood pressure remains normal. The two most common forms of shock are hemorrhagic and septic shock. Both initially present with decreased blood flow, though for different reasons. Thus, monitoring buccal CO2 levels for its increase in a patient at risk for sepsis or bleeding constitutes a reasonable cost-effective early warning monitor. Indeed, buccal CO2 monitoring may represent an ideal tool for a non-invasive monitor that can be applied early so as to target high-risk patient subgroups without fear of iatrogenic complications or false negative results. Buccal CO2 may also be used to titrate resuscitation therapies, although most clinical studies show that the major benefit of any monitoring in septic shock comes from its early identification, triggering early appropriate antibiotic use and initial fluid resuscitation.
